Accelerated Communication Selective Enhancement of b-Adrenergic Receptor Signaling by Overexpression of Adenylyl Cyclase Type 6: Colocalization of Receptor and Adenylyl Cyclase in Caveolae of Cardiac

We investigated the effect of adenovirally mediated overex-pression of adenylyl cyclase type 6 (AC6), a major form of AC expressed in mammalian heart, on G protein-coupled receptor regulation of cAMP production in neonatal rat ventricular myo-cytes. Following gene transfer of AC6, isoproterenol- and for-skolin-stimulated increases in cAMP were markedly enhanced, whereas basal levels of cAMP and responses to several other agonists that stimulate cAMP formation, e.g., prostaglandin E2 (PGE2), H2 agonist, glucagon, and A2 agonist were not in-creased. Studies to test whether the selective enhancement in b-adrenergic receptor (AR) response might result from inhibi-tion of AC6 by Gai and Gbg indicated that pertussis toxin-sensitive inhibition by the muscarinic cholinergic agonist car-bachol was unaltered in myocytes overexpressing AC6